Inhibition of the synthesis and secretion of decidual prolactin by arachidonic acid.
Human decidual explants exposed for 4 h to 150 microM arachidonic acid synthesized and secreted 30.4% (P less than 0.001) and 36.4% (P less than 0.001) less 35S-PRL, respectively, than control explants. Over a 5-h period, the inhibition of PRL secretion was directly proportional to the arachidonic acid concentration at concentrations between 30 and 300 microM (r = 0.91; P less than 0.001). Phospholipase A2 at concentrations of 0.11 and 11.1 U/ml, also inhibited PRL secretion by 46.2 +/- 2.4% (P less than 0.001) and 63.9 +/- 1.4% (P less than 0.001), respectively. Likewise, the fatty acid precursors of arachidonic acid, i.e. linoleic, gamma-linolenic, and dihomo-gamma-linolenic acids, inhibited PRL secretion, but palmitic, oleic, and 11,14,17-icosatrienoic acids and the detergents deoxycholic acid and Triton X-100 had no effects, even at concentrations as high as 300 microM. In contrast, prostaglandins E1, E2, and F2 alpha (3 X 10(-5)-10(12) M each) had no effects on PRL secretion, and the prostaglandin synthetase (cyclooxygenase) inhibitors indomethacin (5 and 25 micrograms/ml) and flufenamic acid (5 micrograms/ml) had no effects on either basal PRL secretion or the inhibitory action of arachidonic acid. These results suggest that arachidonic acid may be involved in the regulation of the synthesis and secretion of decidual PRL. The effect of arachidonic acid, however, does not appear to be mediated by a cyclooxygenase product of arachidonic metabolism.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D003656:Decidua / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005439:Flufenamic Acid / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D010741:Phospholipases A / Q000494:pharmacology; D054467:Phospholipases A2; D011247:Pregnancy; D011388:Prolactin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D005439:Flufenamic Acid; D011388:Prolactin; D010741:Phospholipases A; D054467:Phospholipases A2; D007213:Indomethacin